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Actas Dermo-sifiliograficas 2023Pruritus is the main symptom of many dermatologic and systemic diseases. Atopic dermatitis, psoriasis, contact dermatitis, urticaria, lichen simplex chronicus, mycosis... (Review)
Review
Pruritus is the main symptom of many dermatologic and systemic diseases. Atopic dermatitis, psoriasis, contact dermatitis, urticaria, lichen simplex chronicus, mycosis fungoides, scars, autoimmune diseases, kidney or liver diseases among others are all associated with itch that may require different approaches to management. Although antihistamines seem to be the first line of therapy, in reality their role is limited to urticaria and drug-induced reactions. In fact, the pathophysiologic mechanisms of each of the conditions covered in this review will differ. Recent years have seen the emergence of new drugs whose efficacy and safety profiles are very attractive for the management of pruritus in clinical practice. Clearly we are at a critical moment in dermatology, in which we have the chance to be more ambitious in our goals when treating patients with pruritus.
Topics: Humans; Dermatology; Pruritus; Dermatitis, Atopic; Urticaria; Skin Neoplasms
PubMed: 37003460
DOI: 10.1016/j.ad.2023.03.004 -
The Journal of Allergy and Clinical... 2018Chronic urticaria is defined as the presence of urticaria for a period exceeding 6 weeks, assuming symptoms for most days of the week. It is divided into chronic... (Review)
Review
Chronic urticaria is defined as the presence of urticaria for a period exceeding 6 weeks, assuming symptoms for most days of the week. It is divided into chronic inducible urticarias and chronic spontaneous urticaria, previously termed chronic idiopathic urticaria. The latter designation emphasizes that patients can experience urticaria independent of any exogenous stimulus even if one can define circumstances that may worsen symptoms. A search for such an external "cause" is fruitless because the underlying abnormality is "intrinsic," whether it is autoimmune, or some unknown process. Approximately 40% of patients with chronic spontaneous urticaria report accompanying episodes of angioedema, whereas 10% have angioedema as their primary manifestation. In most cases, it is a self-limiting disorder, persisting for 2 to 5 years in most cases, although 20% of patients suffer for more than 5 years. The treatment that has evolved is largely empiric, based on double-blind, placebo-controlled studies whenever possible, but is not yet targeted to any particular pathogenic mechanism. In this article, we review the current status regarding pathogenesis, discuss the diagnostic workup, and update the approach to treatment including consideration of published guidelines, our own experience, and guideline updates that are being prepared.
Topics: Chronic Disease; Humans; Pruritus; Urticaria
PubMed: 30033911
DOI: 10.1016/j.jaip.2018.04.013 -
Acta Dermato-venereologica Jan 2020Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as... (Review)
Review
Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera-peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.
Topics: Animals; Antipruritics; Humans; Pruritus; Risk Factors; Signal Transduction; Skin; Treatment Outcome; Water Loss, Insensible
PubMed: 31940044
DOI: 10.2340/00015555-3344 -
Journal Der Deutschen Dermatologischen... Oct 2022Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute...
Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org.
Topics: Humans; Antipruritics; Quality of Life; Chronic Disease; Pruritus; Prurigo
PubMed: 36252071
DOI: 10.1111/ddg.14830 -
International Journal of Molecular... Oct 2022Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic... (Review)
Review
Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.
Topics: Humans; Prurigo; Quality of Life; Pruritus; Dermatitis, Atopic; Cytokines
PubMed: 36293248
DOI: 10.3390/ijms232012390 -
Trends in Immunology Dec 2018Relentless, repetitive itching and scratching is a debilitating feature of many chronic inflammatory skin disorders such as atopic dermatitis. While well known... (Review)
Review
Relentless, repetitive itching and scratching is a debilitating feature of many chronic inflammatory skin disorders such as atopic dermatitis. While well known clinically, this itch-scratch cycle has historically lacked in-depth mechanistic understanding. However, recent advances at the interface of itch neurobiology and skin immunology have shed new light on this phenomenon. In this review, we highlight recent advances in our understanding of the neuroimmunology of chronic itch centered around three key points of entry into the itch-scratch cycle: the epithelial barrier, the immune system, and the peripheral nervous system. Furthermore, we explore novel neuro-epithelial-immune interactions that may represent promising therapeutic paradigms.
Topics: Animals; Humans; Peripheral Nervous System; Pruritus
PubMed: 30471983
DOI: 10.1016/j.it.2018.10.001 -
Frontiers in Immunology 2022Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic... (Review)
Review
Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic reactions and anaphylaxis in certain populations. The mechanism of itch is due to introduction of mosquito saliva components into the cutaneous tissue, although the exact pathophysiology is unclear. Histamine is thought to be a key player through mosquito saliva itself or through activation of mast cells by IgE or through an IgE-independent pathway. However, other salivary proteins such as tryptase and leukotrienes may induce non-histaminergic itch. Some individuals have a genetic predisposition for mosquito bites, and people with hematologic cancers, HIV, and other conditions are susceptible to robust reactions. Prevention of mosquito bites is key with physical barriers or chemical repellents. Treatment consists of second-generation antihistamines and topical corticosteroids. Further research on topical treatments that target neural-mediated itch is needed.
Topics: Adrenal Cortex Hormones; Anaphylaxis; Histamine Antagonists; Humans; Immunoglobulin E; Insect Bites and Stings; Pruritus; Tryptases
PubMed: 36211437
DOI: 10.3389/fimmu.2022.1024559 -
The Journal of Clinical Investigation Feb 2023Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here,...
Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produced time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early phase (20 days), CTCL caused hyperinnervations in the epidermis. However, chronic itch was associated with loss of epidermal nerve fibers in the late phases (40 and 60 days). CTCL was also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early and late phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal (i.t.) gabapentin injection reduced late-phase, but not early-phase, pruritus. IL-31 was upregulated in mouse lymphoma, whereas its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in mice with CTCL. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, i.t. administration of a TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.
Topics: Animals; Female; Male; Mice; Lymphoma; Pruritus; Sensory Receptor Cells; Skin; Disease Models, Animal
PubMed: 36520531
DOI: 10.1172/JCI160807 -
American Journal of Clinical Dermatology Jan 2024Chronic prurigo (CPG) is a neuroinflammatory, fibrotic dermatosis that is defined by the presence of chronic pruritus (itch lasting longer than 6 weeks),... (Review)
Review
Chronic prurigo (CPG) is a neuroinflammatory, fibrotic dermatosis that is defined by the presence of chronic pruritus (itch lasting longer than 6 weeks), scratch-associated pruriginous skin lesions and history of repeated scratching. Patients with CPG experience a significant psychological burden and a notable impairment in their quality of life. Chronic prurigo of nodular type (CNPG; synonym: prurigo nodularis) represents the most common subtype of CPG. As CNPG is representative for all CPG subtypes, we refer in this review to both CNPG and CPG. We provide an overview of the clinical characteristics and assessment of CPG, the burden of disease and the underlying pathophysiology including associated therapeutic targets. The information provided results from a PubMed search for the latest publications and a database search for current clinical trials (ClinicalTrials.gov, EU Clinical Trials Register [European Medicines Agency]; using the following terms or combinations of terms: 'chronic prurigo', 'prurigo', 'prurigo nodularis', 'pathophysiology', 'therapy', 'biologics', 'treatment'). Dupilumab is the first authorized systemic therapy by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for CNPG to date. Topical and systemic agents that are currently under investigation in clinical randomized, placebo-controlled phase II and III trials such as biologics (e.g., nemolizumab, vixarelimab/KPL-716, barzolvolimab/CDX-0159), small molecules (ruxolitinib cream, povorcitinib/INCB054707, abrocitinib) and the opioid modulator nalbuphine are highlighted. In the last past 15 years, several milestones have been reached regarding the disease understanding of CPG such as first transcriptomic analysis, first terminology, first guideline, and first therapy approval in 2022, which contributed to improved medical care of affected patients. The broad range of identified targets, current case observations and initiated trials offers the possibility of more drug approvals in the near future.
Topics: Humans; Prurigo; Quality of Life; Pruritus; Antibodies, Monoclonal; Chronic Disease
PubMed: 37717255
DOI: 10.1007/s40257-023-00818-z -
Cells Oct 2020Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent... (Review)
Review
Neurologic insults as varied as inflammation, stroke, and fibromyalgia elicit neuropathic pain and itch. Noxious sensation results when aberrantly increased afferent signaling reaches percept-forming cortical neurons and can occur due to increased sensory signaling, decreased inhibitory signaling, or a combination of both processes. To treat these symptoms, detailed knowledge of sensory transmission, from innervated end organ to cortex, is required. Molecular, genetic, and behavioral dissection of itch in animals and patients has improved understanding of the receptors, cells, and circuits involved. In this review, we will discuss neuropathic itch with a focus on the itch-specific circuit.
Topics: Humans; Inflammation; Neuralgia; Neurons; Perception; Pruritus
PubMed: 33050211
DOI: 10.3390/cells9102263